Exposure to a Western‐Style Diet During Early Development Reduces Skeletal Muscle Lipid Metabolism and CI‐dependent Oxidative Capacity in Juvenile Non‐Human Primate Offspring

Maternal obesity and diabetes during pregnancy is linked to an increased and earlier risk for offspring to develop insulin resistance and metabolic diseases. We have previously found in a non‐human primate model that maternal western‐style diet (WSD) alone or in combination with obesity reduces oxidative capacity in fetal muscle concomitant with increased oxidative damage and lipid metabolism. The purpose of this study was to determine whether fetal adaptations to maternal WSD alone independent of maternal obesity leads to persistent reductions in skeletal muscle metabolism in juvenile offspring prior to the development of obesity.Experimental DesignLean adult female Japanese macaques were maintained on a control diet (CTR) or WSD prior to and during pregnancy and lactation. Male and female offspring were than weaned to independent housing at 7 mo and fed a WSD or CTR resulting in four groups (CTR/CTR, CTR/WSD, WSD/CTR and WSD/WSD). Insulin sensitivity was measured by i.v. GTT and body composition by DEXA at 36 mo. Muscle biopsies were taken at 40 mo to measure oxidative metabolism by high resolution respirometry and electron transport system complex (C) activities by spectrophotometry. Data were analyzed by a 2‐way ANOVA (maternal diet X offspring diet)ResultsThere were no differences in body weight, % fat or insulin sensitivity across groups. Total oxidative capacity and CI‐dependent oxidative capacity were decreased by ~30% (P=0.001) in the presence of lipid substrates in gastrocnemius (gastroc) and soleus of offspring exposed to a maternal WSD independent of offspring diet. CI‐specific activity was reduced by 50% (P<0.0001) in the gastroc. Citrate synthase activity was not different suggesting that reduced oxidative metabolism is not caused by diminished mitochondrial abundance.ConclusionsMaternal WSD during pregnancy and lactation results in a persistent reduction in skeletal muscle lipid metabolism in offspring prior to offspring obesity. Switching offspring to a heathy diet did not ameliorate the effects of developmental exposure to maternal WSD. Impaired muscle lipid metabolism is linked to insulin resistance in adults and likely contributes to the increased risk of metabolic disease in exposed offspring.Support or Funding InformationR24 DK090964R01 MH107508R01 (ES)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.